1. Field of the Invention
This invention is directed to alkyl cyanoacrylate compositions which are specifically formulated for topical application onto intact or broken human skin. The compositions of this invention are further formulated for single or repeated/intermittent use and are resistant to premature polymerization.
2. State of the Art
Cyanoacrylates are well known in the art and can be represented by formula I: ##STR1##
wherein R is an alkyl or other suitable substituent. Such cyanoacrylates are disclosed in U.S. Pat. Nos. 3,527,224; 3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,826. Typically, when applied onto living tissue, the R substituent is alkyl of from 2 to 10 carbon atoms and most often is butyl (e.g., n-butyl).
Suggested uses for alkyl cyanoacrylate compositions include their use in topical application onto intact skin in order to form a polymer layer which inhibits blister and pressure ulcer formation as described in U.S. Pat. No. 5,306,490 and U.S. patent application Ser. No. 08/082,927 U.S. Pat. No. 5,403,591. Still other suggested uses includes inhibiting irritation arising from prosthetic devices as described in U.S. patent application Ser. No. 08/200,953 as well as inhibiting skin irritation and infection due to incontinence as described in concurrently filed U.S. patent application Ser. No. 08/299,935, U.S. Pat. No. 5,580,565, entitled "USE OF CYANOACRYLATE ADHESIVES FOR PROVIDING A PROTECTIVE BARRIER FILM FOR THE SKIN". The disclosures of such patent and patent applications being incorporated herein by reference in their entirety. When so employed, the cyanoacrylate adhesive composition is applied topically onto intact skin and, after curing, a cyanoacrylate polymer coating is formed which coating adheres strongly to the skin.
Other uses of alkyl cyanoacrylates include their use with small wounds as described in U.S. patent application Ser. No. 08/231,638 where the cyanoacrylate composition is applied onto the surface of a topical wound (one which does not penetrate the dermal layer) where, after curing, a protective coating or layer is formed over the wound. The disclosure of this application is also incorporated herein by reference in its entirety.
Ideally, for topical applications as recited above, the alkyl cyanoacrylate compositions should meet as many of the following criteria as possible:
(1) the alkyl cyanoacrylate composition should be formulated to be stable against premature polymerization. Such formulations would therefore be suitable for storage in applicators for multiple use applications and in spray applicators where unintended polymerization can clog the spray mechanism; PA1 (2) the alkyl cyanoacrylate composition should be of suitable viscosity for desired application onto the skin; PA1 (3) once applied to the skin, the alkyl cyanoacrylate should not polymerize so quickly as to generate sufficient heat as to impart a "burning" sensation to the patient but should cure within from about 10 seconds to about 1 minute after application; PA1 (4) the resulting cured polymer should possess sufficient flexibility such that the integrity of the polymer coating is not compromised by, for example, cracking, etc; PA1 (5) the resulting cured polymer should possess sufficient durability such that the polymer does not prematurely shed from the patient's skin; and PA1 (6) is non-toxic when applied to skin. PA1 (a) from about 75 to 82 weight percent of an alkyl cyanoacrylate; PA1 (b) from about 50 to 500 parts per million of SO.sub.2 as a polymerization inhibitor; and PA1 (c) from about 18 percent to about 25 percent by weight of a biocompatible plasticizer PA1 wherein the alkyl cyanoacrylate, in monomeric form, is represented by formula I: ##STR2## PA1 (a) from about 75 to 80 weight percent of n-butyl cyanoacrylate; PA1 (b) about 200 parts per million of SO.sub.2 as a polymerization inhibitor; and PA1 (c) from about 20 percent to about 25 percent by weight of a dialkyl phthalate independently having from 1 to 10 carbon atoms in each alkyl group PA1 wherein the n-butyl cyanoacrylate, in monomeric form, is represented by formula I: ##STR3## PA1 where R is selected from the group consisting of alkyl of 2 to 10 carbon atoms. Partial polymers (i.e., oligomers) of such cyanoacrylates are also encompassed within this definition.
In contrast to topical applications, it is also known that alkyl cyanoacrylate compositions can be employed in surgical environments as suture replacements or hemostats. When employed in these environments, the parameters of the alkyl cyanoacrylate composition for such applications often diverge from the compositional parameters for topical application. For example, unlike topical application over large areas of skin, surgical application of the alkyl cyanoacrylate composition is typically over very specific, small total surface area internal parts of the human body and, accordingly, parameters such as viscosity, curing time, flexibility, durability, etc., are often different for this application as opposed to the parameters required for topical application. Accordingly, while it is recognized in the Robertson, et al., U.S. Pat. No. 3,722,599 to combine a polymerization inhibitor, a thickener, and a plasticizer with a fluoroalkyl cyanoacrylate, these compositions are disclosed for use as suture replacements or as hemostats and such compositions are not always suitable for topical application onto the skin surface.